Iohexol belongs to the class of non-ionic contrast media. Together with iopamidol, it is one of the most used products in diagnostic x-ray procedures, since it presents a number of advantages over other contrast media, mainly in terms of tolerability.
Since X-ray inspections usually require a large amount of product (up to 200 g per patient), it derives that purity is fundamental for biomedical use.
The last step of the chemical synthesis of iohexol, as disclosed in U.S. Pat. No. 4,250,113 and subsequent patent-literature, is an alkylation reaction in a basic environment on an amide with an alkyl halide di-hydroxylated: 
This inevitably leads to the development of O-alkylated by-products (O-alkylates), which are very difficult to eliminate due their resemblance to iohexol. Numerous methods of iohexol purification are described in literature. U.S. Pat. No. 4,250,113 discloses the use of butanol as the final crystallization solvent, but said technique is not completely effective in eliminating the O-alkylates.
EP919540 discloses that ethanol crystallization can reduce the content in O-alkylate substances. Nevertheless, the examples provided show that, in the best case, the 1.3% initial content in O-alkylates is reduced to 0.55%. The purification value thus obtained is just slightly lower than the limit fixed by European Pharmacopea (0.6%).
U.S. Pat. No. 5,204,086 discloses that the crystallization with i-PrOH is effective in eliminating the O-alkylate impurities from iohexol only by 25÷30%.
In WO9808804, methoxy-ethanol and mixtures thereof with isopropanol are used both in iohexol crystallization and in the last step. Nevertheless, the examples provided show that said technique is scarcely effective in eliminating the O-alkylate substances, the 0.68% initial value thereof being reduced to 0.51%.
Further, the methoxy-ethanol can cause damages to the reproductive system, sterility and foetal malformations.
As a matter of fact, there is still a great need for an easy, sure and effective method for the elimination of iohexol impurities, particularly O-alkylates.